Dott Andrea RossiClinica Geriatrica

Azienda Ospedaliera Universitaria

Integrata di Verona

Metodiche strumentali per la valutazione della massa

muscolare

Ferrara, 19 Ottobre 2013

Incontro Società Medico Chirurgica di Ferrara La sarcopenia: definizioni, patogenesi e

trattamento

““Sarcopenia is a term that denotes the Sarcopenia is a term that denotes the

decline in muscle massdecline in muscle mass and and strength that occurs with healthy aging.strength that occurs with healthy aging.””

Rosenberg, Am J Clin Nutr 1989

““Sarcopenia is part of normal agingSarcopenia is part of normal agingand does not require a disease to occur,and does not require a disease to occur,

although it is accellerated by chronic diseases.although it is accellerated by chronic diseases.””

Roubenoff et al, J Gerontol 2000

Age and Ageing 2010; 39: 412Age and Ageing 2010; 39: 412––423423

Criteria for the diagnosis of sarcopeniaDiagnosis is based on documentation of criterion 1 plus

(criterion 2 or criterion 3).

11-- Low muscle massLow muscle mass2-Low muscle strength

3- Low physical performance

Cruz-Jentoft Alfonso J et al Sarcopenia: European Consensus on Definition and Diagnosis. Report of the European Working Group on Sarcopenia in Older People- Age and Ageing,2010 ;

1-12

•Methods for muscle mass in vivo with muscle

metabolites

•Nuclear techniques for quantifyng muscle mass in vivo

•Bioelettrical Impedance analysis and Air-

displacement plethysmography system

•Most used Radiographic methods for quantifyng

muscle mass in vivo

OBJECTIVES:

Modello a tre compartimenti, massa magra non Modello a tre compartimenti, massa magra non ossea (2), massa grassa (1), massa ossea (3)ossea (2), massa grassa (1), massa ossea (3)

GRASSO GRASSO (1)(1)

ACQUAACQUA

PROTEINEPROTEINE

GLICOGENOGLICOGENO

MINERALIMINERALI

MASSA MASSA OSSEA OSSEA (3)(3)

Adapted from Hoffman DJ et al. In press

MASSA MAGRA

NON OSSEA (2)

MASSAMAGRA=FFM

PESO CORPOREO

TESSUTONON OSSEO

The reference man and woman

International Commision on Radiological protection (IRCP); Report of the task group on reference man. Oxford Pergamon Press

Heymsfield SB; Human body composition, II edition Cap 14; 2005

•comprende massa muscolare scheletrica (400 muscoli) + liscia +cardiaca

Massa Muscolare

•soprattutto nelle gambe, meno in braccia, tronco e testa

Distribution of skeletal muscle cross sectional are a (MRI CSA) measurements per slice (10 men and 10 women)

Abe T. Br J Sports Med 2003;37:436–440

39%

10%

37%

14%

methods for muscle mass in vivomethods for muscle mass in vivowith muscle metabolites with muscle metabolites

•Creatinina

•3-Metilistidina

Relation between total-body skeletal muscle mass (S M)measured by computerized axial tomography (CT) and 24-h

creatinineexcretion (n = 12).

Wang Z et al. Am J Clin Nutr 1996;63:863-9©2003 by American Society for Nutrition

SM = 18.9 X Cr + 4.1CV: 8-9%

Influence of dietary protein and creatine on urinar y creatinine excretion (n = 6).

Heymsfield et al. Am J Clin Nutr 1983;37:478-494©2003 by American Society for Nutrition

Creatinina• È un precursore della creatina a livello epatico e

renale (Borsook and Dubnoff 1947).

• 1 grammo di creatinina escreta corrisponde a 18-20 kg massa muscolare (Talbot 1938; Cheek 1968)

Limitationi:• C’è un ampia variabilità individuale di

escrezione di creatinina giornaliera in relazione in particolare all’introito alimentare.

• Altri fattori posso alterare la misurazione: età, sesso, livello di attività fisica e profilo metabolico.

3-Metilistidina

• 3-Metilistidina (3-MH) è un aminoacido che è misura del catabolismo delle proteine muscolari. La sua concentrazione nel muscolo umano è relativamente costante tra i 4 e i 65 anni, ma cala con la riduzione dell’escrezione urinaria legata all’età.

Wang Z et al. JPEN J Parenter Enteral Nutr 1998 22: 82

Total body skeletal muscle mass (SM. in kilograms) measured bycomputerized axial tomography (CT) (ordinate) vs 24 -hour urinary

3-methylhistidine excretion (3-MH, W micromoles) (n = 10)

Wang Z et al. JPEN J Parenter Enteral Nutr 1998 22: 82

SMLukaski=0.118 x 3-MH-3.45

Total body skeletal muscle mass measured by the Luka ski equation(SM , in kilograms) on the ordinate vs total body ske letal muscle massmeasured by multiscan computerized axial tomography ( CT) method

--8.9 Kg 8.9 Kg

3-MHLimitazioni:• L’uso di 3-MH come marker di massa

muscolare è stata criticata in considerazione della potenziale influenza del turnover di proteine non muscolari (Rennie and Millward 1983).

• È stato evidenziato contributo di proteine provenienti da cute e tratto gastrointestinale rispetto all’escrezione urinaria di 3MH.

• La misurazione richiede dieta priva di carne per permettere l’eliminazione di quota endogena di 3-MH.

Nuclear techniques for quantifyng Nuclear techniques for quantifyng muscle mass in vivomuscle mass in vivo

•Total body potassium

K40 - Whole Body Counting• K40 emette radiazione gamma• Usando contatori total body la quantità

di radiazioni emesse può essere determinata

• Assunzioni:– frazione constante di K40 nel

potassio corporeo (0.0118%)– frazione costante di potassio nella

massa non grassa

Total-body skeletal muscle (SM) measured by magneti c resonance imaging plotted against total body potassium (TBK) measured by

whole-body 40K counting.

Wang Z et al. Am J Clin Nutr 2003;77:76-82©2003 by American Society for Nutrition

MR

I

SM (kg) = 0.0085 × TBK (mmol)

Changes in total body potassium (TBK) with age in 9 73 Changes in total body potassium (TBK) with age in 9 73 men (1200 observations). men (1200 observations).

He Q et al. Am J Clin Nutr 2003;78:72-77©2003 by American Society for Nutrition

• Tecnica non invasiva non richiede digiuno

• Dai 20 ai 40 minuti ad esame.

• Precisione:5% per gli adulti. 8-12% nei bambini.

• 180 centri al mondo (la metà negli USA).

• Costo dipende da età della popolazione esaminata

• Costo dell’esame nell’adulto $10,000-15,000.

• Costo di camera schermata dove eseguire l’esame è di $80,000.

K40 - Whole Body Counting

Most used methods for quantifyng Most used methods for quantifyng muscle mass in vivomuscle mass in vivo

•Air-displacement plethysmography system

•Bioelettrical Impedance analysis

AirAir --Displacement Plethysmography (BOD POD) Displacement Plethysmography (BOD POD)

Pricipio fisico: legge dei gas di Boyle e MariotteA temperatura costante il volume (V) occupato da un a determinata massa è inversamente proporzionale alla pressione cu i quella massa èsottoposta

Calcola il volume, quindi il PS; per ottenere la ma ssa adiposa si usa la Formula di SIRI: Massa adiposa% = (4950/densità-4,5 )100Dove: densità FM = 900 kg/m 3; densità FFM= 1100 kg/m 3

Oscillazioni 6/min

•Range di errore è dell’ 2% simile alla bilancia idrostatica•Richiede 5 minuti•Può ospitare soggetti fino ai 400 kg•È formula dipendente•Scarsa trasportabilità ed estremamente costosa

AirAir --Displacement Plethysmography (BOD POD)Displacement Plethysmography (BOD POD)

Vantaggi e svantaggi

Bioelectrical impedance assessment (BIA)Bioelectrical impedance assessment (BIA)

Janssen I, J Appl Physiol 2001

•Sviluppato negli anni 60•Una corrente a basso voltaggio (50 kHz 800 µA max) viene fatta passare attraverso il corpo del paziente

Organismo vivente

Fluidi extra-cellulari

=

Conduttori

Membrane cellulari

=

Condensatori

Attraversandoli la corrente incontra una:

La forza con cui si oppongono al passaggio della corrente:

Resistenza Reattanza

BIOIMPEDENZIOMETRIA: modello bicompartimentale Consente di stimare l’ Acqua Corporea Totale

Corrente

Resistenza è maggiore nel tessuto grasso (14-22% acqua)Conduttanza è maggiore nel tessuto magro (73% acqua) che quindi offrirà minore

resistenza

Correlation of skeletal muscle mass as evaluted on the basis of the regression equation derived and measured with M RI

(388 men and women, aged 18–86 yr)

Janssen I et al. J Appl Physiol 2000;89:465-471

©2000 by American Physiological Society

Equazione di Janssen: MM = [(Ht2/R x 0.401) + (sesso + 3.825) + (età x –0.071)] + 5.102

MM = massa muscolare scheletrica, Ht= altezza, R= resistenza

Difference between skeletal muscle mass measured by MRI and BIA vs. average skeletal muscle mass

measured by the 2 methods for the Caucasian subject s.

Janssen I et al. J Appl Physiol 2000;89:465-471

Distribution of relative differences between MRI-me asured and BIA-predicted skeletal muscle mass within the Caucasian subjects.

Janssen I et al. J Appl Physiol 2000;89:465-471

©2000 by American Physiological Society

Vantaggi della BIAVantaggi della BIA

• non è richiede molta esperienza ed abilità• strumentazione è portatile• investimento e spese di manutenzione

relativamente basse • misurazione sul paziente è indolore e rapida

Svantaggi della BIASvantaggi della BIA

• altamente influenzata dallo stato di idratazione del soggetto

• influenzata da temperatura ambientale• Non permette di distinguere massa magra

appendicolare• è formula dipendente

Most used Radiographic methods Most used Radiographic methods for quantifyng muscle mass in vivofor quantifyng muscle mass in vivo

•Dual Energy X-ray absorptiometry

•Computed Tomography

•Magnetic Resonance

Dual energy XDual energy X--Ray absorptiometry Ray absorptiometry

DXA DXA

Dual Energy XDual Energy X --ray Absorptiometryray Absorptiometry

Sorgente a Raggi X (produce fotoni a due diversi livelli di energia con differenti profili di attenuatione)

Fotoni Collimatore (pinhole for pencil beam, slit for fan beam)

Soggetto

Detettore

(1)(1)

(2)(2)

(3)(3)

MASSA MASSA GRASSA (1)GRASSA (1)

ACQUAACQUA

PROTEINEPROTEINE

GLICOGENOGLICOGENO

MINERALIMINERALI

MASSAMASSA

OSSEA (3)OSSEA (3)

MASSA MASSA MAGRA MAGRA

NON NON OSSEA (2)OSSEA (2)

Dual-energy X-ray Absorpiometry (DXA)

Fonte di raggi X

Filtro Tessuti = R

40 KeV

70 KeV

rapporto fra il valore di attenuazione subito dal raggio

a più bassa energia (A) e quello subito dal raggio a

energia più elevata (B). Tale rapporto risulta tanto più

elevato quanto più alto è il numero atomico della

sostanza attraversata.

R

A

B

dove

Dual-energy X-ray Absorpiometry (DXA)

-

-

-

-

5 10 15 20

3.5

3.0

2.5

2.0

1.5 -

1.0

R

Numero atomico

HC N

O

NaMg

PSCl

K

Ca

----

Massa Grassa

Massa Magra

Minerale Osseo

I trigliceridi (= massa grassa), essendo costituiti da H, C e O, hanno il minimo valore di

R; i liquidi intra ed extra-cellulari (=massa magra), contenenti Na, K e Cl, hanno valori di

R intermedi. L’osso minerale e i cristalli di idrossiapatite hanno i valori più elevati di R.

Total body. Womenkg 104, BMI 34

Brownbill RA and Ilich JZ, 2004

Total body. Women59 kg, BMI 22.6

TOTAL BODY Dual-energy X-ray Absorpiometry (DXA)

Correlation between total-body skeletal muscle (SM) mass estimated by magnetic resonance imaging and appendicular lean soft tissue (ALST)

mass estimated by dual-energy X-ray absorptiometry in men (•) and women ( ○) in the model-development group.

Kim J et al. Am J Clin Nutr 2002;76:378Kim J et al. Am J Clin Nutr 2002;76:378 --383383

©2002 by American Society for Nutrition

Correlation between the difference in measured and predicted total-body skeletal muscle (SM) mass and the mean of measured and predicted SM mass

in men (•) and women ( ○) in the model-validation group.

©2002 by American Society for Nutrition

Kim J et al. Am J Clin Nutr 2002;76:378Kim J et al. Am J Clin Nutr 2002;76:378 --383383

Location of computed tomography (CT) slices and are as used in dual-energy X-ray absorptiometry (DEXA) scan analys is to

measure leg skeletal muscle mass.

Visser M et al. J Appl Physiol 1999;87:1513-1520

©1999 by American Physiological Society

A–D: relationship between muscle mass by fan-beam D EXA and by multislice CT in elderly men ( ●) and women ( ○) at 4 leg regions.

Visser M et al. J Appl Physiol 1999;87:1513-1520

A–D: difference in muscle mass between fan-beam DEX A and by multislice CT plotted against the mean at 4 leg reg ions.

Visser M et al. J Appl Physiol 1999;87:1513-1520

Weight and dimensions limits of different DXA Weight and dimensions limits of different DXA modelsmodels

Manufacturer/ Densitometer

Weight Limit kg (lb)

Table Dimensions cm

GE Lunar Prodigy Advance

159 (350) 197.5 × 60

GE Lunar Prodigy 136 (300) 197.5 × 60

GE Lunar DPX-MD 136 (300) 196.8 × 57.6

Hologic QDR series 136 (300) 195.6 × 65- 67

Hologic Discovery Series

159 (350) 195.6 × 67

Norland XR-46 114 (250) 193 × 64

Norland XR-36 114 (250) 193 × 64

Brownbill RA, Ilich JZ; BMC medical Imaging; 2005

Hologic Discovery Series (2010) 204 Kg 195 × 65

GE Lunar iDXA (2010) 182 Kg 287 × 132

Comparison between Dexa Hologic QDR 2000 Comparison between Dexa Hologic QDR 2000 and 4500and 4500

Ellis KJ, Shypailo RJ; J Bone Min Res; 1998

Advantages and disadvantages of DXAAdvantages and disadvantages of DXA

• Advantagesx-ray exposure is minimal (< 1 mrem for 1 scan) subregion evaluation is allowedquick: total body scan

• Pencil beam DXA (20-25 min)• Fan beam DXA (< 4-4.5 min)

used in large clinical trialsHighly precise and reproducible technique (CV for fat mass 1-1.7% and for FFM 0.7-1.0%)

• Disadvantagescosts (machine and technicians)not transportablelose accuracy with incresing body thickness, than lose precision and accuracy in thicker obese subjectsradiation exposure (as a day of sunbathing)weight and dimensions limits

CT scan

-1000 -190 -30 +30 +80 +1000

Air Adiposetissue

Muscle Bone

_ _ _ _ _ _CT can differentiate tissues based on their attenuation

characteristics, which depend on their density.

X-ray attenuation is quantified as Hounsfield Units (HU).

0

_

Low density High density

Hounsfield units:>200 HU for bone-30 to -190 HU for AT 0 to 100 HU for muscle

CT analysis with Sliceomatic Region Growing Mode Abdomen and Thigh

Intermuscular Fat (CT)

Goodpaster et al., 2006

LDLTLDLT women, 69 year, BMI 49, W 121 cm, diabetes

Muscle density (Hounsfield unit) - average value of muscle = lean, f at, collagen, blood vessels– lower density means more fat

Myosteatosis – muscle density and/or intramuscular fat University of Verona

Modificazione della composizione corporea della coscia valutate mediante TAC (n=1981) in 5 anni di follow-up

Infiltrazione lipidica del muscolo (cm2)

10

15

20

25

30

Basale 5 anni

P<0.001

Rossi AP et al. J Geront 2011

200

210

220

230

240

250

Basale 5 anni

Area del muscolo (cm2)

P<0.001

Computer Tomography (CT)Computer Tomography (CT)

Advantages Cross-sectional measurement of lean and fat areas in a specific part of the bodyEvaluation of muscle quality parameters (intermuscular fat)Relatively rapid (approx 30 min for whole body scan)Can be used for longitudinal studiesLow frequency of artifacts compared to MRI

DisadvantagesExposure to radiation Time- consumingHigh space to requirementsTechnically difficult to performExpensive

Magnetic Resonance Imaging (MRI)

Image 1 Image 46Image 24

Appendicular protocol Appendicolar protocolAbdominal rotocollo

Heymsfield S, Ross R, Wang Z Handbook of Obesity; 2000

Illustration of typical images of arm and leg as ob tained by magnetic resonance imaging (MRI), computerized tomo graphy

(CT), and cadaver (Cad).

Mitsiopoulos N et al. J Appl Physiol 1998;85:115-12 2

Comparison of typical in vivo magnetic resonance images obtained on 2 separate days from the same

subject at the level of the midthigh.

©1998 by American Physiological SocietyMitsiopoulos N et al. J Appl Physiol 1998;85:115-12 2

Regression analyses among MRI, CT, and Cad for Skeletal muscle

©1998 by American Physiological SocietyMitsiopoulos N et al. J Appl Physiol 1998;85:115-12 2

Regression analyses among MRI, CT, and Cad for interstitial adipose tissue

Mitsiopoulos N et al. J Appl Physiol 1998;85:115-12 2

Magnetic Resonance Imaging (MRI)Magnetic Resonance Imaging (MRI)Advantages Does not use ionizing radiation High quality image and can accurately quantify both subcutaneous & visceral fatRelatively rapid (approx 30 min for whole body scan)Can be used for longitudinal studies

DisadvantagesNot available appropriate image analysis softwareLess precise for intermuscular fat quantificationSome exclusions (e.g. pacemakers)ExpensiveHigh frequency of artifacts (“shading” at the peripheries of images due to inhomogeneity in the magnetic field)

Comparison of methods for assessing Comparison of methods for assessing skeletal muscle massskeletal muscle mass

Creatinine TBK- DXA MRI CT ANTH BIA/3-MH TBN

Accurate?

Reproducible?

Cost to purchase?

Cost to operate?

Technician training?

Radiation exposure?

Site WBWB WBWB R,WBR,WB R,WBR,WB R,WBR,WB R,WBR,WB R(?),WBR(?),WB

Trasportable?

Lukaski H; Human body composition, II edition Cap 1 4; 2005